Neonatal Lymphopenia Screening Is Important for Early Diagnosis of Severe Combined Immunodeficiency

Abstract

Objective T-cell receptor excision circles are expensive for neonatal severe combined immunodeficiency screening in developing countries. We aimed to detect immunodeficiencies presenting with lymphopenia to enable screening in the general population and to improve awareness regarding lymphopenia among clinicians. Study Design This study was conducted prospectively. In all newborns included, complete blood count from umbilical cord blood samples was recorded. Absolute lymphopenia was defined as absolute lymphocyte count <3,000/mm3 in umbilical cord blood sample. Complete blood count was repeated at month 1 in cases found to have lymphopenia. Results Overall, 2,000 newborns were included in the study. Absolute lymphopenia was detected in 42 newborns (2.1%), while lymphocyte count was >3,000/mm3 in 1,958 newborns (97.9%). Two infants with persisted lymphopenia at the end of the first month; therefore, further evaluations such as lymphocyte subsets for severe combined immunodeficiency (SCID) were done. In the first infant, the lymphocyte subgroups were detected as compatible with T (−), B (−), natural killer cells (NK) (+) SCID phenotype RAG defect. Sanger sequencing revealed that NM_000448 c.2209C > T (p.R737C) homozygous mutation of RAG1 gene. In the other infant, the lymphocyte subgroups were found as considered with T (−), B (+) NK (−) SCID phenotype JAK3 defect. Both patients underwent hematopoietic stem cell transplantation from human leukocyte antigen-matched family member. Conclusion Absolute lymphopenia by complete blood count is a more simpler, relatively noninvasive and inexpensive screening methodfor detection of SCID in newborns compared with T-cell receptor excision circles technique. Key Points

Current Status of Newborn Bloodspot Screening Worldwide 2024: A Comprehensive Review of Recent Activities (2020–2023)

“…Also, near the end of 2022, a Turkish molecular diagnostics startup launched an exome-sequencing-based newborn DNA screening test, which has the potential to become a suite of tests for various genetic diseases [ 1059 ]. Other recent reports concerning Turkish NBS have been published: a study of lymphopenia screening from cord blood demonstrating a cheaper, less invasive alternative to TREC analyses for SCID [ 1060 ]; a report of the status of genetic diagnostic laboratories and the frequency of genetic variants associated with CF detected through the Turkish NBS program [ 1061 ]; a 5-year data review of CF screening in a tertiary care center showing low sensitivity and PPV and a need for a national study to establish new cutoff values [ 1062 ]; a 6-year data review of the CF NBS protocol also showing low PPV in 3 tertiary care facilities with a similar appeal for re-evaluation of the screening protocol [ 1063 ]; and a report showing that mothers in Turkey are not sufficiently knowledgeable about NBS and recommending that education using mass media, educational environments (pregnancy schools), and screening test centers (including increasing awareness of this deficiency among midwives and nurses) [ 1064 ]. Most recently, a report on case reviews noted that ENBS can also play a pivotal role in identifying conditions in mothers of newborns identified by NBS [ 1065 ].…”

Adenosine Deaminase (ADA)-Deficient Severe Combined Immunodeficiency Unmasked by Persistent Lymphopenia and Prolonged Severe SARS-CoV-2 Infection in a Three-Week-Old Neonate

“…In our case, the persistent lymphopenia even with normal immunoglobulin levels, the persistent COVID-19 PCR positivity, the development of opportunistic co-infections, and the rapid clinical deterioration were all suggestive of SCID. This case shows that absolute lymphopenia can be used as a simple and inexpensive screening method for SCID in newborns and children in general [ 3 ], especially in countries where T-cell receptor excision circles (TRECs) are not included in newborn screening like the UAE. Moreover, it shows that normal immunoglobulin levels do not rule out immunodeficiency in infants less than 6 months of life as maternal immunoglobulins are still not weaned.…”

Case Report: Mutations in JAK3 causing severe combined immunodeficiency complicated by disseminated Bacille Calmette–Guérin disease and Pneumocystis pneumonia

“…Neonatal PID screening programs, such as T cell receptor excision circles (TREC)-based newborn screening ( 2 ), have been deployed in some developed countries/regions ( 8 ) but unfortunately not in mainland China. However, absolute lymphopenia (i.e., absolute lymphocyte count <3,000/mm 3 ) in a newborn complete blood count should alert us to screen for and exclude SCID ( 27 ).…”